The PmrAB System-inducing Conditions Control Both Lipid A Remodeling and O-antigen Length Distribution, Influencing the Salmonella Typhimurium-Host Interactions

JUAN V. FARIZANO; PESCARETTI MM,; LOPEZ, FE; FONG-FU HSU; DELGADO MA

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2012 vol. 287 p. 38778 - 38789

0021-9258

The Salmonella enterica serovar Typhimurium lipopolysaccharide consisting of covalently linked lipid A, non-repeating core oligosaccharide, and the O-antigen polysaccharide is the most exposed component of the cell envelope. Previous studies demonstrated that all of these regions act against the host immunity barrier. The aim of this study was to define the role and interaction of PmrAB-dependent gene products required for the lipopolysaccharide component synthesis or modification mainly during the Salmonella infection. The PmrAB two-component system activation promotes a remodeling of lipidAand the core region by addition of 4-aminoarabinose and/or phosphoethanolamine. These PmrAdependent activities are produced by activation of ugd, pbgPE, pmrC, cpta, andpmrGtranscription. In addition, underPmrAregulator activation, the expression of wzzfepE and wzzst genes is induced, and their products are required to determine the O-antigen chain length. Here we report for the first time that Wzzst protein is necessary to maintain the balance of 4-aminoarabinose and phosphoethanolamine lipid A modifications. Moreover, we demonstrate that the interaction of the PmrA-dependent pbgE2 and pbgE3 gene products is important for the formation of the short O-antigen region. Our results establish that PmrAB is the global regulatory system that controls lipopolysaccharide modification, leading to a coordinate regulation of 4-aminoarabinose incorporation and O-antigen chain length to respond against the host defense mechanisms.